Lipoic acid has been found to be a coenzyme of alpha-keto acid dehydrogenases involved in cellular respiration. Although these enzymes are present in most cells, there is no dietary requirement for lipoic acid in normal healthy animals, indicating that synthesis takes place in the body. The objectives of one part of the proposed studies are to: 1. determine the precursors of lipoic acid, 2. determine the biosynthetic pathway, using the chick embryo as the biological model, and 3. more importantly, determine the interrelationship of lipoic acid biosynthesis and the diseases of genetic and/or environmental (including nutritional) nature. It is proposed that varying cellular levels of lipoic acid may have influence on cellular respiration, glycolysis, fat and cholesterol metabolism, especially as they are related to atherosclerosis. Investigations will be carried out to test the hypothesis that decreased rate of lipoic acid synthesis, either genetically or malnutritionally, affects these parameters in such a manner as to increase an animal's susceptibility to atherosclerosis and to coronary heart diseases. If such is found to be true, lipoic acid may have a beneficial therapeutic effect in preventing these diseases. A new chemical method for the determination of lipoic acid in biological tissues is being developed in my laboratory. This method will permit studies to be carried out with the genetic atherosclerosis-susceptible and -resistant strains of chicks and Japanese quail to determine the effect of dietary lipoic acid on blood cholesterol and atherosclerosis.